Residue-orientation-dependent dynamics and selectivity of active pocket in microbe class I terpene cyclases

Jingyuan Zhuang, Fan Zhang, Jingwei Zhou, Wenbin Deng, Ruibo Wu

Research output: Contribution to journalArticlepeer-review


Microbe class I terpene cyclases (TPCs) are responsible for deriving numerous functionally and structurally diverse groups of terpenoid natural products. The conformational change of their active pockets from “open” state to “closed” state upon substrate binding has been clarified. However, the key structural basis relevant to this active pocket dynamics and its detailed molecular mechanism are still unclear. In this work, on the basis of the molecular dynamics (MD) on two microbe class I TPCs (SdS and bCinS), we propose that the active pocket dynamics is highly dependent on the residue orientation of two conserved structural bases R-D dyad and X-R-D triad, rather than the previously suggested flexibility of kink region. Actually, we considered that the flexibility of kink region is synchronous with the R residue orientation of the X-R-D triad, which could regulate the entrance size of active pocket and thus affect the substrate selectivity of active pocket by utilizing the promiscuity of the X-R-D triad. Furthermore, to better understand the function of the two structural bases, two intelligible models of “PPi catcher-locker” and “selector-PPi sensor-orienter” are proposed to, respectively, describe the R-D dyad and X-R-D triad and broadened to more microbe class I TPCs. These findings exhibit the dynamics of active pocket inaccessible in static crystal structures and provide useful structural basis knowledge for further design of microbe class I TPCs with different cyclization ability.

Original languageEnglish (US)
Pages (from-to)4985-4994
Number of pages10
JournalJournal of Chemical Information and Modeling
Issue number10
StatePublished - Oct 26 2020
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences


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